PROJECT SUMMARY Lymphatic filariasis (LF) is a mosquito-transmitted, neglected tropical disease (NTD) affecting over 120 million people living in 72 countries. Current control strategies for LF infection which rely on annual mass drug administration (MDA) to the ?at-risk? populations has failed to interrupt disease transmission partly due to chronic reinfection. There is no licensed prophylactic vaccine currently available for the LF, and of those tested over the last 2 decades have advanced beyond rodent testing. This is partly because of poor protection, but also due to lack of resources to advance the technology given its truly neglected nature. We have developed and established the first successful multivalent recombinant fusion protein (Bm-HAXT) for the prophylaxis of LF called LFGuard?. This vaccine is comprised of a protein antigen, Bm-HAXT, formulated with the TLR4 agonist GLA-on-Alum. When formulated, our vaccine is highly stable and provides nearly sterile immunity in rodents (>95%) and significant protection in non-human primates (70%). To date LFGuard? has been extensively tested and confirmed for its prophylactic potential and safety in different animal models such as mice (n=980), Mongolian gerbils (jirds) (n=220), and rhesus macaques (n=60). In addition to treatment of LF, LFGuard? has also shown significant promise in dogs as a vaccine for heartworms. This SBIR Phase 2 proposal will allow us to move LFGuard? into pre-clinical development including GMP manufacture, vialing, and stability and efficacy testing. A clinical study and a supporting toxicology study will be designed, and stability will be confirmed through both short- and long-term stability programs. Finally, we will conduct a pre-IND meeting with the FDA prior to execution of the toxicology study. When these studies are complete, this important antigen will be poised to enter the first human clinical trials for the first ever lymphatic filariasis vaccine. We propose the following aims for this SBIR Phase 2 grant: (1) Manufacture of BmHAXT under cGMPs (2) Perform pre-clinical IND-enabling studies.